Many important cell and tissue functions depend on the surface presentation of molecules, so it is critical to determine the chemical state (composition, molecular structure, and orientation) as well as the distribution of biological moieties present on a surface and in the near surface region of biomedical devices. Thus, it is essential to develop surface analysis techniques capable of providing quantitative and detailed surface chemical state information at high spatial resolutions, both for 2-D and 3-D imaging of biological materials. Time-of-flight secondary ion mass spectrometry (ToF-SIMS), with its high chemical specificity and spatial resolution, is an excellent method for obtaining this information. However, until commercial cluster ion beam sources became readily available in the last 5-10 years, ToF-SIMS analysis was limited to analyzing the outer ~2nm of biological materials. This is because the commercial high-energy, monoatomic ion sources available on the initial ToF-SIMS instruments (Ga+, Cs+, etc.) resulted in significant sample degradation and loss of molecular information during sputtering. Several years ago commercial cluster ion sources such C60+ became available. These sources were capable of molecular depth profiling of biological materials and opened the possibility of 3-D imaging with ToF-SIMS. In late 2010 the manufacturer of our ToF-SIMS instrument at the University of Washington (IONTOF) introduced two new cluster ion beam sources for their TOF.SIMS 5 instrument (a new Ar cluster ion source and significantly upgraded C60 cluster ion source). The Ar cluster ion source offers significant advantages over previous cluster ion sources (significantly improved depth resolution and applicability to a wider range of materials). The new C60 cluster ion source offers significant improvements over our existing C60 source (2x increase in ion energy, as well as significant enhancements in both mass and spatial resolution). To capitalize on these new capabilities and the benefits they will provide to NIH- funded research projects, we are requesting $374,604.80 to upgrade our existing IONTOF TOF.SIMS 5 instrument with the new cluster ion beam sources. The National ESCA and Surface Analysis Center for Biomedical Problems (NESAC/BIO, NIH grant EB-002027) will provide an additional $50,000 for the purchase of these ion sources. Research projects that will benefit from the new capabilities of the Ar and C60 cluster ion beam sources include analysis of medical implants (e.g., drug-loaded/coated stents), biofilms, cell sheets, tissue sections, tissue engineering scaffolds, microarray devices (DNA, antibody, carbohydrate, etc.), biosensors, etc. PUBLIC HEALTH RELEVANCE: Knowledge about biomedical implant surfaces and an understanding of how these surfaces interact and direct biological processes when such a device is placed in the body is needed to permit the rational design of new and improved biomedical implants. The proposed cluster ion beam sources will provide new information about the surface properties of biomedical devices, as well as the biomolecules and cells interacting with those devises, that is needed to achieve this objective.